Other Recent Studies

Role of the Pou4 (Brn3) and Islet transcription factors in the development of the brainstem, spinal cord and sensory systems

In a seminal series of studies between 1995 and 2011, we defined the essential role of the transcription factors Brn3a and Islet1 in the differentiation of peripheral sensory neurons and brainstem. These studies included innovative use of microarrays and chromatin immunoprecipitation to define gene regulatory programs in transgenic mice. Our interest in the habenula began with a project in which identified Brn3a as a key regulator of habenula development (medial plus lateral), required for the distinctive pattern of gene expression in this region. This study, and the resulting collaboration with the Allen Institute for Brain Science, provided the basis for the experimental models we use to study habenula function. A few examples of the resulting publications follow:

Hmx1 is a transcription factor gene known to regulate external ear development in mice, rats and cattle, and is responsible for oculoauricular syndrome (OAS) in humans. We first identified Hmx1 as a downstream target of Brn3a in the developing trigeminal ganglion. In Quina, et al., 2012a, we defined the role of this factor in cranial ganglion development. In collaborative work with the Cox laboratory here at CDBRM we identified a mutation in an ultraconserved enhancer in rats that phenocopies Hmx1 loss of function, one of only a few known examples of enhancer mutations that have clear Mendelian inheritance.

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